Purpose of review: Antiangiogenic therapy is now a standard in first line for metastatic renal cell carcinoma. Among the different options, sunitinib is particularly proposed by most guidelines, as well as a combination of bevacizumab and interferon-alfa. Defining second line therapy after these agents is dependent on indirect data since no phase III trial has specifically addressed that question.
Recent findings: The most relevant data point to everolimus that has been proven to improve PFS with acceptable toxicity compared with best supportive care in a phase III trial. Most studies on the use of antiangiogenic therapies after failure of a first one seem to demonstrate, more than anything else, that the most effective antiangiogenic therapy should be used up front since limited benefit is expected in second line.
Summary: This paper presents some relevant data to help recommend the most appropriate second-line therapy. The quality of data on everolimus is sufficient to propose its use for most patients in the second line setting after failure of a vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI). Studies on a second line of antiangiogenic therapy demonstrate limited efficacy that does not lead to a recommendation of adequacy for most patients.